The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases.

BACKGROUND: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). PATIENTS AND METHODS: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. RESULTS: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. CONCLUSIONS: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Sentinel node biopsy by indocyanine green retention fluorescence detection for inguinal lymph node staging of anal cancer: preliminary experience.

BACKGROUND: There is some evidence that sentinel lymph node (SLN) biopsy guided by dye injection and/or radioisotopes can improve staging of inguinal lymph nodes (LNs) in anal cancer. This study was performed to investigate the feasibility of fluorescence detection of SLN and lymphatic mapping in anal cancer. METHODS: Twelve patients with anal cancer without evidence for inguinal LN involvement were included in the study. Intraoperatively, all patients received a peritumorous injection of 25 mg indocyanine green (ICG) for fluorescence imaging of the SLN with a near-infrared camera. For comparison, conventional SLN detection by technetium-(99)m-sulfur radiocolloid injection in combination with blue dye was also performed in all patients. The results of both techniques and the effect on the therapeutic regimen were analyzed. RESULTS: Overall, ICG fluorescence imaging identified at least one SLN in 10 of 12 patients (detection rate, 83%). With the combination of radionuclide and blue dye, SLN were detected in 9 of 12 patients (detection rate, 75%). Metastatic involvement of the SLN was found in 2 of 10 patients versus 2 of 9 patients. Patients with metastatic involvement of the SLN received extended radiation field with inguinal boost. CONCLUSIONS: ICG fluorescence imaging allows intraoperative lymphatic mapping and transcutaneous SLN detection for selective biopsy of inguinal SLN in anal cancer. This technique should be further evaluated in comparative studies with larger patient numbers.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Potential target antigens for immunotherapy in human pancreatic cancer.

BACKGROUND: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. METHODS: Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. RESULTS: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. CONCLUSIONS: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.

Indolent stage IE non-Hodgkin's lymphoma of the orbit: results after primary radiotherapy.

AIMS: Primary non-Hodgkin's lymphoma (NHL) of the orbit is uncommon, representing approximately 8% of extranodal NHLs. Twenty-two patients with indolent stage IE NHL were reviewed retrospectively to analyze the outcome and late effects of primary local radiotherapy. MATERIALS AND METHODS: The median age at first diagnosis was 63.5 years (range 24-82 years). Extranodal mucosa-associated lymphoid tissue lymphoma (n = 15) was the most common histological subtype of NHL, followed by follicular (n = 6) and lymphoplasmacytic lymphoma (n = 1). Radiotherapy was performed using a linear accelerator. The median radiation dose was 40 Gy (range 30-46 Gy). None of the patients received chemotherapy before irradiation. The follow-up period was 62 months (range 8-136 months). RESULTS: A complete response was achieved in all patients. The 5-year local control rate was 100%. Distant relapse occurred in 2 patients, resulting in a 5-year distant relapse-free survival rate of 88%. The 5-year overall survival rate was 89%; there were no lymphoma-related deaths. No serious acute complications (grade 3/4) were observed. Grade 1/2 late effects were documented in 44% of patients. Grade 3 complications (cataract: 2, dryness: 2) were observed in 4 patients (18%). CONCLUSIONS: Indolent early stage orbital NHL can be controlled with local radiotherapy. Morbidity is low. Regular follow-up examinations are necessary to detect rare cases of distant relapse.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518).

BACKGROUND: Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. METHODS/DESIGN: The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. DISCUSSION: The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.

Piezosurgery--a new safe technique in cranial osteoplasty?

All surgical interventions on the neurocranium bear the risk of injury of the dura mater and development of a cerebrospinal fluid fistula. Therefore, despite careful preparation, damage to the dura mater cannot always be omitted. Especially after surgery and in patients with increased intracranial pressure (craniosynostoses) there is a high risk of perforating the dura. In this article a new surgical technique for osteotomy (Piezosurgery) that avoids perforation of the dura is presented. Ultrasonic microvibrations allow a selective cut of only mineralized structures without damage to the soft tissue. Even in case of accidental contact the dura remains undamaged. This advantage is also useful for bone splitting, to separate the tabula externa from the tabula interna in situ, without any risk of dura perforation even in case of the very thin bones in an infantile skull. The present work shows the applicability of piezoelectric surgery in high-risk patients after osteotomy, avoiding perforation of the dura mater.

[Advances in radio-oncology. From precision radiotherapy with photons to ion therapy with protons and carbon ions]. / Fortschritte in der Radioonkologie. Von der Präzisionsstrahlentherapie mit Photonen zur Ionentherapie mit Protonen und Kohlenstoffionen.

Modern techniques in radiation oncology, such as fractionated stereotactic radiotherapy (FSRT), stereotactic radiosurgery (SRS) or intensity modulated radiotherapy (IMRT) allow the application of high local doses to defined treatment volumes, while normal structures in close vicinity can be spared; high local control rates can be achieved, while treatment-related toxicity can be minimized. Innovative Hi-Art tomotherapy systems offer an alternative, combining a 6 MV photon accelerator with a CT scanner. Ion beams, such as protons and carbon ions, have been shown to be beneficial for distinct tumor entities. Both offer a characteristic physical dose distribution with an inverse dose profile contributing to beneficial dose conformality. Carbon ions also offer the advantage of increased relative biological effectiveness. For certain tumor types, a significant increase in local control and survival rates could be obtained with carbon ions.

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

BACKGROUND: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. METHODS/DESIGN: The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. DISCUSSION: The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.

Daytime pulsed dose rate brachytherapy as a new treatment option for previously irradiated patients with recurrent oesophageal cancer.

The aim of this study was to evaluate the feasibility, effects, and toxicity of pulsed dose rate (PDR) brachytherapy for re-irradiation of oesophageal carcinoma. A total of 16 patients (median age 67 years) with inoperable recurrences from oesophageal cancer after primary radio-(chemo)-therapy (median 50 Gy) were re-irradiated using PDR brachytherapy ((192)Ir, 37 GBq). Treatment was carried out on an outpatient basis applying a weekly 5 Gy daytime schedule (0.5 Gy pulse(-1) h(-1), total dose 15-20 Gy). The dose was prescribed 10 mm from the mid-dwell position and encompassed the clipped tumour extension with 2 cm margins. The use of clips for delineation of tumour extent and catheter movement during irradiations was evaluated. All 61 PDR treatments were applied safely. The median catheter movement was 5 mm, range 2-12 mm. After a median follow-up of 8 months, three patients had a complete and five a partial remission. Body weight increased in 5 of 16 (31%) and was stable in 4 of 16 (25%) patients, respectively. The median grade 2 (RTOG/EORTC) dysphagia-free survival was 17 months. Seven patients experienced grade 1, five grade 2, and one grade 3 late toxicity. Three patients with uncontrolled locoregional disease showed grade 4 complications (oesophago-tracheal fistulae (n=2), fatal arterial bleeding (n=1). Daytime PDR brachytherapy proved to be feasible and provided effective palliation. Toxicity remains a major problem. Thus, total dose should be restricted to <15 Gy in this palliative situation.

Concentration of transforming growth factor beta in human bone tissue: relationship to age, menopause, bone turnover, and bone volume.

Transforming growth factor beta (TGF-beta) is thought to play an important role in bone metabolism, but its relationship to human bone turnover and bone mass has not been examined yet. In this study, we measured the concentration of TGF-beta in 811 samples of male and female bone from four representative sites of the human skeleton and in the supernatants of 72 short-term human bone marrow cultures from the iliac crest. The concentrations of TGF-beta1 and TGF-beta2 in the bone matrix were positively correlated with histomorphometric indices of bone resorption and bone formation and with serum levels of osteocalcin and bone-specific alkaline phosphatase. We also observed a positive association between the release of TGF-beta in the bone marrow cultures and serum osteocalcin. Changes in the rate of cancellous or cortical bone remodeling with age or menopause were accompanied by corresponding changes in skeletal TGF-beta. In contrast, there was no significant relationship between the concentration of TGF-beta and bone volume at any skeletal site. In conclusion, our study supports the hypothesis that TGF-beta plays an important role in human bone remodeling, but fails to demonstrate an association between the skeletal concentration of TGF-beta and human bone mass.

Differential effects of platelet-derived growth factor isoforms on plasminogen activator activity in fetal rat osteoblasts due to isoform-specific receptor functions.

We examined receptor binding and metabolic effects of the platelet-derived growth factor (PDGF) isoforms AA, AB, and BB in cultures of osteoblastic cells from fetal rat calvaria. Saturation binding experiments demonstrated the presence of 6,000 binding sites for PDGF-AA, 42,000 for PDGF-AB, and 60,000 for PDGF-BB. Binding competition experiments were compatible with the recently postulated model of three PDGF receptor subtypes with differential affinity for the PDGF isoforms. The effects of the PDGF isoforms on DNA synthesis, collagen synthesis, and alkaline phosphatase activity in osteoblasts strictly correlated with the number of available binding sites. Accordingly, PDGF-BB was the most potent isoform, PDGF-AB was slightly less potent, and PDGF-AA was the least potent. In contrast, we found that PDGF-BB was less potent than PDGF-AB in increasing plasminogen activator activity in the osteoblast-conditioned medium. Our data strongly suggest that the PDGF receptor subtypes in fetal rat osteoblasts not only selectively bind one or more PDGF isoforms, but are also capable of responding differently to these isoforms.

Age-related changes in insulin-like growth factor I and II in human femoral cortical bone: lack of correlation with bone mass.

The concentration of insulin-like growth factor-I (IGF-I) in human cortical bone declines with age, but the relevance of this decline for cortical bone turnover and bone mass is unknown. In the present study, we simultaneously assessed the concentration of IGF-I and -II in cortical bone matrix and histomorphometric parameters of bone mass and bone turnover in 125 samples from the proximal human femur shaft. Bone width decreased by 27% and porosity increased by 100% in female cortical bone between the fourth and the ninth decade. Similar, but weaker, changes tended to occur in male cortical bone. The concentrations of both IGF species were correlated with the percentage of osteons undergoing bone remodeling. However, despite age-related decreases in both IGF species in men and in IGF-I in women, neither of the IGFs accounted for age-related or age-independent variability in cortical porosity or bone width. In conclusion, these data suggest that the local concentrations of IGF-I and -II are related to cortical bone turnover. In contrast, our study provides no evidence for a major role of bone matrix IGF-I and -II as determinants of cortical bone mass in elderly individuals. Whether other components of the IGF system may be stronger determinants of cortical bone loss remains to be determined.

Results of chest wall reirradiation using pulsed-dose-rate (PDR) brachytherapy molds for breast cancer local recurrences.

PURPOSE: We report in a retrospective study on the effect and toxicity of chest wall reirradiation using pulsed-dose-rate (PDR) afterloading molds. METHODS AND MATERIALS: Between 1993 and 1999, a total of 58 patients were treated. All patients presented with locally recurrent breast cancer (31 patients had concomitant distant metastases) after mastectomy and a previously completed course of radiation therapy (median, 54 Gy; range, 36-70). Indication for reirradiation was a progressive macroscopic skin recurrence in 30 cases and an incomplete surgical resection in 28 patients. Standard treatment consisted of a split course with two fractions of 20 Gy (interval, 31 days). The reference dose was prescribed to the skin surface at 5 mm distance from the source. PDR brachytherapy (37 GBq, (192)Ir) was carried out after geometric distance optimization with 0.5-1 Gy/pulse/h. The irradiated median area was 423 cm(2) (range, 100-919). The median follow-up was 18 months (range, 7-84). RESULTS: The actuarial 1-, 2- and 3-year local recurrence-free survival rates in patients treated for macroscopic disease (microscopic disease in parenthesis) were 89% (96%), 81% (85%), and 75% (71%). Local control was obtained in 24/30 (22/28) patients. Twenty-nine of the 34 patients (85%) who deceased during follow-up were locally controlled. 9/58 patients experienced Grade III acute toxicity, 35/58 patients Grade III (29/58 telangiectasia, 6/58 contracture), and 4/58 Grade IV late toxicity (RTOG/EORTC). CONCLUSION: Reirradiation of the chest wall using PDR brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.

Correlation of intraoperatively irradiated volume and fibrosis in patients with soft-tissue sarcoma of the extremities.

PURPOSE: To investigate the influence of intraoperatively irradiated volume on soft-tissue fibrosis. METHODS AND MATERIALS: Fifty-three patients with soft-tissue sarcoma of the extremities were treated with intraoperative radiotherapy (IORT) (median dose 15 Gy) and postoperative fractionated therapy (median dose 46 Gy). The median follow-up was 41.5 months (range 18-94). Late toxicity was classified according to the LENT-SOMA criteria. A Cox regression model was calculated to identify the parameters that could influence soft-tissue fibrosis Grade 3 or 4. Five parameters were observed: extent of surgical procedure, IORT in case of recurrence, extent of IORT volume, extent of IORT dose, and extent of postoperative volume. In addition, a logistic regression model was calculated to demonstrate the relationship between the IORT volume and fibrosis development. RESULTS: The overall survival rate after 5 years was 84%. The actuarial tumor control rate was 90% after 5 years. Eleven patients developed soft-tissue fibrosis. Five patients developed Grade 3 fibrosis and 1 patient developed Grade 4 fibrosis. Only the IORT volume had a significant influence on Grade 3 or 4 fibrosis development. An IORT volume of 210 cm(3) conveyed a 5% risk (confidence interval 1-20%) of the development of severe fibrosis. The risk of severe Grade 3 or 4 fibrosis increased to 50% (confidence interval 15-80%) if a volume of 420 cm(3) was irradiated. CONCLUSION: The effect of volume in patients treated with IORT was remarkable. The ratio of side effects was relatively low. The risk of soft-tissue Grade 3 or 4 fibrosis increased with the extent of the IORT volume. Compared with the literature, IORT provides excellent local control in these patients.

HDR-brachytherapy boost for residual tumour after external beam radiotherapy in patients with tracheal malignancies.

Seven inoperable patients with tracheal neoplasms received a high dose rate (HDR) brachytherapy boost (median 15 Gy, single dose 3-5 Gy) for residual tumour after external beam radiotherapy (median 50 Gy, 5 x 2 Gy/week). The median actuarial survival was 34.3 months. The 1-, 2- and 3-year actuarial survival rates were 85.7%, 85.7% and 32%. Local control was obtained in 5/7 patients. Late toxicity occurred in three patients (stenosis n = 2, hemorrhage n = 1). Our data indicate, that a HDR brachytherapy boost is effective and feasible.